SUMMARY Chronically activated leukocytes recruited to premalignant tissues functionally contribute to cancer development; however, mechanisms underlying pro- versus anti-tumor programming of neoplastic tissues by immune cells remain obscure. Using the K14-HPV16 mouse model of squamous carcinogenesis, we report that B cells and humoral immunity foster cancer development by activating Fcγ receptors (FcγRs) on resident and recruited myeloid cells. Stromal accumulation of autoantibodies in premalignant skin, through their interaction with activating FcγRs, regulate recruitment, composition, and bioeffector functions of leukocytes in neoplastic tissue, which in turn promote neoplastic progression and subsequent carcinoma development. These findings support a model in which B cells, humoral immunity, and activating FcγRs are required for establishing chronic inflammatory programs that promote de novo carcinogenesis.

To examine whether hospital-based physical therapy is associated with functional changes and early hospital readmission among hospitalized older adults with community-acquired pneumonia and declining physical function. Study design was a retrospective observation study. Participants were community-dwelling older adults admitted to medicine floor for community-acquired pneumonia (n = 1,058). Their physical function using Katz activities of daily living (ADL) Index declined between hospital admission and 48 hours since hospital admission (Katz ADL Index 6→5). The intervention group was those receiving physical therapy for ≥ 0.5 hour/day. Outcomes were Katz ADL Index at hospital discharge and all-cause 30-day hospital readmission rate. The intervention and control groups did not differ in the Katz ADL Index at hospital discharge (p = 0.11). All-cause 30-day hospital readmission rate was lower in the intervention than in control groups (OR = 0.65, p = 0.02). Hospital-based physical therapy has the benefits toward reducing 30-day hospital readmission rate of acutely ill older adults with community-acquired pneumonia and declining physical function.Key words: hospitalization, patient outcome assessment, physical therapy, pneumonia Functional decline in older adults is common and occurs in up to one-third of recently hospitalized older adults [1]. The hospital environment accelerates the reduction of functional reserve implicated factors include forced immobilization, disorientation due to unfamiliar hospital environments, and frequent orders not to eat by mouth [2][3][4][5][6]. In fact, hospitalized older adults spend more than 70% of their time lying in bed due to acute medical conditions, despite having the ability to walk [4].Functional decline during or after hospitalization is associated with adverse health outcomes, prolonged hospital stays due to more frequent occurrences of hospital complications, such as delirium; and more frequent episodes of early hospital readmissions and even higher long-term mortality rate [7][8][9][10][11][12].

Abstract Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér–Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=−0.42, n=28, p=0.031 and rs=−0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=−0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.

The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen' s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.

Background Chronic pain from temporomandibular disorders remains an undertreated condition with debate regarding the most effective treatment modalities. Objective The aim of the study was to investigate the treatment effect of an internet-based multimodal pain program on chronic temporomandibular disorder pain and evaluate the feasibility of a larger randomized controlled trial. Methods An unblinded randomized controlled pilot trial was conducted with 43 participants (34 females, 9 males; median age 27, IQR 23-37 years) with chronic temporomandibular pain. Participants were recruited within the Public Dental Health Service and randomized to intervention (n=20) or active control (n=23). The intervention comprised a dentist-assisted internet-based multimodal pain program with 7 modules based on cognitive behavior therapy and self-management principles. The control group received conventional occlusal splint therapy. Primary outcomes included characteristic pain intensity, pain-related disability, and jaw functional limitation. Secondary outcomes were depression, anxiety, catastrophizing, and stress. Outcomes were self-assessed through questionnaires sent by mail at 3 and 6 months after treatment start. Feasibility evaluation included testing the study protocol and estimation of recruitment and attrition rates in the current research setting. Results Only 49% of participants (21/43) provided data at the 6-month follow-up (internet-based multimodal pain program: n=7; control: n=14). Of the 20 participants randomized to the internet-based multimodal pain program, 14 started treatment and 8 completed all 7 modules of the program. Between-group analysis showed no significant difference for any outcome measure at 3- or 6-month follow-up—characteristic pain intensity (3 months: P=.58; 6 months: P=.41), pain-related disability (3 months: P=.51; 6 months: P=.12), jaw functional limitation (3 months: P=.45; 6 months: P=.90), degree of depression (3 months: P=.64; 6 months: P=.65), anxiety (3 months: P=.93; 6 months: P=.31), stress (3 months: P=.66; 6 months: P=.74), or catastrophizing (3 months: P=.86; 6 months: P=.85). Within-group analysis in the internet-based multimodal pain program group showed a significant reduction in jaw functional limitation score at the 6-month follow-up compared to baseline (Friedman: χ2=10.2, P=.04; Wilcoxon: z=–2.3, P=.02). In the occlusal splint group, jaw function limitation was also reduced at the 6-month follow-up (Friedman: χ2=20.0, P=.045; Wilcoxon: z=–2.3, P=.02), and there was a reduction in characteristic pain intensity at the 3- and 6-month follow-up (Friedman: χ2=25.1, P=.01; Wilcoxon 3 months: z=–3.0, P=.003; Wilcoxon 6 months: z=-3.3, P=.001). Conclusions This study was not able to demonstrate a difference in treatment outcome between an internet-based multimodal pain program and occlusal splint therapy in patients with chronic temporomandibular pain. However, the findings suggested that the internet-based multimodal pain program improves jaw function. The results also confirmed the treatment effect of occlusal splint therapy for chronic temporomandibular pain. Furthermore, because of the high attrition rate, this pilot study showed that a randomized controlled trial with this design is not feasible. Trial Registration ClinicalTrials.gov NCT04363762; https://clinicaltrials.gov/show/NCT04363762